**1. Introduction: cardiovascular associated with metabolic syndrome**

Syndrome X or Insulin resistance syndrome is also known as metabolic syndrome (MetS). It is defined as the concurrence of obesity-associated cardiovascular risk factors inclusive of abdominal obesity, impaired glucose tolerance, hypertriglyceridemia and hypertension [1]. Meanwhile, CVD is a heart and circulatory system disease that is currently one of the main causes of morbidity and mortality worldwide. They are the series of heterogeneous diseases, like most commonly caused by CVD atherosclerosis and chronic diseases that evolve progressively over a lifetime, and are asymptomatic for a long period of time [2]. It is world leading cause of death worldwide, and 17.9 million people died every year with high record from developed and developing countries. In 2017, World Health Organization (WHO) list out diseases related to CVD such as coronary heart disease (CHD), cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism [3].

In addition, Ford et al. [4] stated that MetS is a syndrome had a link with 3–5 coronary heart disease (CHD) risk factors and increases the incidence of cardiovascular events especially among the elderly population. Some studies have shown that MetS is 1.50–2.00 times more common in individuals with CHD and significantly increases frequency of cardiovascular events, progress and risk of consequences [5, 6]. The risk of CHD is 7 times higher among individuals with MetS and diagnosed diabetes mellitus [7]. On the other hand, obesity plays a major role as an underlying risk factor for cardiovascular disease and changes in cardiac function associated with obesity have been described as "obesity cardiomyopathy".

Besides that, the relation between obesity and metabolic risk factors is growing rapidly. Across the globe, obesity and related metabolic disorders are becoming significant health care issues. Obesity pathogenesis involves the balance between consumed calories and energy expenditure, followed by body weight maintenance. The complex process of weight loss involves the interaction of diet, physical activity, environmental, behavioral and physiological factors, as there are several hormones and peptides involved in the regulation of appetite, eating behavior and energy expenditure [8]. In addition, chronic increase in body weight and adiposity in the cardiovascular system can lead to significant neuro-hormonal changes and adaptations.

These alterations include renin-angiotensin-aldosterone system activation, altered adipocytokine and pro-inflammatory cytokine levels, and sympathetic nervous system activation. These inflammatory products are produced in abnormal quantities in the event of obesity. Any of these items has been involved in affecting one of the metabolic risk factors or another related to MetS. Activation of the sympathetic nervous system can contribute to the commonly described increase in heart rate, retention of renal sodium, circulating blood volume, end-diastolic ventricular volume, cardiac output, and blood pressure. More generally, vascular and cardiac function abnormalities (vasoconstriction, tachycardia) and metabolic balance abnormalities (excess lipolysis driving the level of fatty acids, peripheral and hepatic insulin resistance induced by catechol) can be simultaneously driven by activation of the sympathetic nervous system [1].

#### **2. Regulation of food intake and appetite**

Food intake plays a role as a transportation for food supply which modulated by metabolic drive generated for energy requirement. While appetite is a psychological desire to eat which related to the energy balance model of weight regulation by involving in various aspects of eating pattern such as frequency of eating, serving portion, type of food and palatability of food [9]. The complex interactions between hormones from gastrointestinal tract and the hypothalamus involve particular regions where hormones interact to create feelings of appetite and satiety that can lead to the food intake or a feeling of fullness beyond the metabolic

**95**

tissue hormones.

*The Mechanistic and Pathophysiological Role of Adiponectin and Resistin towards Regulation…*

needs [10]. Meanwhile, homeostatic system plays an important role in balance the energy expenditure and food intake that contribute to the stability of body fat

Generally, ingestion of food started in the oral cavity and taste receptor. The taste of sour, sweet, salty, bitter and savory will be validated by G-protein-coupled receptors by sending the information via blood circulation to the brain. In the stomach, Brain-derived neurotrophic factor (BDNF) and neurotrohin-3 are known as neurotrophic factor helping in innervating of the stomach wall during nutrient storing. Ghrelin is a hormone sending an important signal during empty stomach and rapidly suppressed upon the ingestion of food. Bloodstream is a major route of ghrelin to the brain to control the appetite. In the intestine area, fat, protein and glucose from food intake will enhance enteroendocrine cells and adipocyte to release hormones for the digestion and absorption process with various signaling pathways involved [12]. Enterendocrine cells produced the gut hormones such as glucagon-like peptide 1 (GLU-1), cholecystokinin (CCK) and glucose-dependent insulinotropic polypeptide which rapidly secreted into bloodstream or distributed

There are many theories to explain about appetite mechanism such as Glucostat theory, Dual-centre theory, Aminostatic theory and Lipostat theory [14]. In 1950 [15], Mayer proposed the Glucostat theory which states that the drop in blood glucose level below than the threshold regulates the neuronal activity for the food intake. This theory regulates short-term control over appetite. However, this theory had been largely abandoned in 1970 due to the failure of finding any correlation between arteriovenous blood glucose concentration with hunger rate and food

Next, dual-centre theory involved with two centre of brain known as Ventro medial hypothalamus (VMH) and Lateral hypothalamus (LH) which related to blood glucose level (**Figure 1**). Hunger state will be induced by LH in producing ghrelin hormone which trigger by the drop of blood glucose level while after taking meal blood glucose level will be raise and activate VMH to initiate satiety state. In addition, VMH is potentially found to develop over eating which can lead to

In 1956, Mellinkoff [20] proposed the aminostatic theory involving the production of amino acid after protein stores breakdown sends signals to the brain for energy balance. Muscle catabolism activities caused high amino acid production and stimulate eating behavior while satiety will be reached by diminished level of amino acids [14]. However, it should be noted that evidence of such regulation or the existence of "protein-stat" is not extensive; mainly because of the concept has

Lipostat theory explains the activity of adipose tissues undergo lipolysis in generate fatty acids and glycerol. Both lipolysis products will be circulated in the blood and brain for energy expenditure maintenance. High rate of lipolysis will lead to increase in food consumption and post prandial will decrease lipolysis as resulted in its termination [14]. Adipocytokines play an important role in orexigenic pathway which enhance the food intake and anorexigenic pathway which inhibit the food intake. In 1994, Zhang et al. [22] had discovered leptin as primary adipose tissue-derived factor secreted from white adipose tissue and acts on hypothalamus to induce satiety in regulating food intake and energy expenditure [23] while adiponectin have opposite functions of leptin. Various experiments have done and accepted that leptin is a signal that conveys information from the periphery to the brain regarding the long-term state of the body's energy stores [21, 24, 25]. Lipostat is not limited to leptin mechanism only but it is involved with all type of adipose

*DOI: http://dx.doi.org/10.5772/intechopen.96171*

content over time [11].

as local messengers [13].

intake [16–18].

obesity [14, 19].

not been a target for investigation [21].

#### *The Mechanistic and Pathophysiological Role of Adiponectin and Resistin towards Regulation… DOI: http://dx.doi.org/10.5772/intechopen.96171*

needs [10]. Meanwhile, homeostatic system plays an important role in balance the energy expenditure and food intake that contribute to the stability of body fat content over time [11].

Generally, ingestion of food started in the oral cavity and taste receptor. The taste of sour, sweet, salty, bitter and savory will be validated by G-protein-coupled receptors by sending the information via blood circulation to the brain. In the stomach, Brain-derived neurotrophic factor (BDNF) and neurotrohin-3 are known as neurotrophic factor helping in innervating of the stomach wall during nutrient storing. Ghrelin is a hormone sending an important signal during empty stomach and rapidly suppressed upon the ingestion of food. Bloodstream is a major route of ghrelin to the brain to control the appetite. In the intestine area, fat, protein and glucose from food intake will enhance enteroendocrine cells and adipocyte to release hormones for the digestion and absorption process with various signaling pathways involved [12]. Enterendocrine cells produced the gut hormones such as glucagon-like peptide 1 (GLU-1), cholecystokinin (CCK) and glucose-dependent insulinotropic polypeptide which rapidly secreted into bloodstream or distributed as local messengers [13].

There are many theories to explain about appetite mechanism such as Glucostat theory, Dual-centre theory, Aminostatic theory and Lipostat theory [14]. In 1950 [15], Mayer proposed the Glucostat theory which states that the drop in blood glucose level below than the threshold regulates the neuronal activity for the food intake. This theory regulates short-term control over appetite. However, this theory had been largely abandoned in 1970 due to the failure of finding any correlation between arteriovenous blood glucose concentration with hunger rate and food intake [16–18].

Next, dual-centre theory involved with two centre of brain known as Ventro medial hypothalamus (VMH) and Lateral hypothalamus (LH) which related to blood glucose level (**Figure 1**). Hunger state will be induced by LH in producing ghrelin hormone which trigger by the drop of blood glucose level while after taking meal blood glucose level will be raise and activate VMH to initiate satiety state. In addition, VMH is potentially found to develop over eating which can lead to obesity [14, 19].

In 1956, Mellinkoff [20] proposed the aminostatic theory involving the production of amino acid after protein stores breakdown sends signals to the brain for energy balance. Muscle catabolism activities caused high amino acid production and stimulate eating behavior while satiety will be reached by diminished level of amino acids [14]. However, it should be noted that evidence of such regulation or the existence of "protein-stat" is not extensive; mainly because of the concept has not been a target for investigation [21].

Lipostat theory explains the activity of adipose tissues undergo lipolysis in generate fatty acids and glycerol. Both lipolysis products will be circulated in the blood and brain for energy expenditure maintenance. High rate of lipolysis will lead to increase in food consumption and post prandial will decrease lipolysis as resulted in its termination [14]. Adipocytokines play an important role in orexigenic pathway which enhance the food intake and anorexigenic pathway which inhibit the food intake. In 1994, Zhang et al. [22] had discovered leptin as primary adipose tissue-derived factor secreted from white adipose tissue and acts on hypothalamus to induce satiety in regulating food intake and energy expenditure [23] while adiponectin have opposite functions of leptin. Various experiments have done and accepted that leptin is a signal that conveys information from the periphery to the brain regarding the long-term state of the body's energy stores [21, 24, 25]. Lipostat is not limited to leptin mechanism only but it is involved with all type of adipose tissue hormones.

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

with obesity have been described as "obesity cardiomyopathy".

activation of the sympathetic nervous system [1].

**2. Regulation of food intake and appetite**

hypertriglyceridemia and hypertension [1]. Meanwhile, CVD is a heart and circulatory system disease that is currently one of the main causes of morbidity and mortality worldwide. They are the series of heterogeneous diseases, like most commonly caused by CVD atherosclerosis and chronic diseases that evolve progressively over a lifetime, and are asymptomatic for a long period of time [2]. It is world leading cause of death worldwide, and 17.9 million people died every year with high record from developed and developing countries. In 2017, World Health Organization (WHO) list out diseases related to CVD such as coronary heart disease (CHD), cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism [3]. In addition, Ford et al. [4] stated that MetS is a syndrome had a link with 3–5 coronary heart disease (CHD) risk factors and increases the incidence of cardiovascular events especially among the elderly population. Some studies have shown that MetS is 1.50–2.00 times more common in individuals with CHD and significantly increases frequency of cardiovascular events, progress and risk of consequences [5, 6]. The risk of CHD is 7 times higher among individuals with MetS and diagnosed diabetes mellitus [7]. On the other hand, obesity plays a major role as an underlying risk factor for cardiovascular disease and changes in cardiac function associated

Besides that, the relation between obesity and metabolic risk factors is growing rapidly. Across the globe, obesity and related metabolic disorders are becoming significant health care issues. Obesity pathogenesis involves the balance between consumed calories and energy expenditure, followed by body weight maintenance. The complex process of weight loss involves the interaction of diet, physical activity, environmental, behavioral and physiological factors, as there are several hormones and peptides involved in the regulation of appetite, eating behavior and energy expenditure [8]. In addition, chronic increase in body weight and adiposity in the cardiovascular system can lead to significant neuro-hormonal changes and

These alterations include renin-angiotensin-aldosterone system activation, altered adipocytokine and pro-inflammatory cytokine levels, and sympathetic nervous system activation. These inflammatory products are produced in abnormal quantities in the event of obesity. Any of these items has been involved in affecting one of the metabolic risk factors or another related to MetS. Activation of the sympathetic nervous system can contribute to the commonly described increase in heart rate, retention of renal sodium, circulating blood volume, end-diastolic ventricular volume, cardiac output, and blood pressure. More generally, vascular and cardiac function abnormalities (vasoconstriction, tachycardia) and metabolic balance abnormalities (excess lipolysis driving the level of fatty acids, peripheral and hepatic insulin resistance induced by catechol) can be simultaneously driven by

Food intake plays a role as a transportation for food supply which modulated by metabolic drive generated for energy requirement. While appetite is a psychological desire to eat which related to the energy balance model of weight regulation by involving in various aspects of eating pattern such as frequency of eating, serving portion, type of food and palatability of food [9]. The complex interactions between hormones from gastrointestinal tract and the hypothalamus involve particular regions where hormones interact to create feelings of appetite and satiety that can lead to the food intake or a feeling of fullness beyond the metabolic

**94**

adaptations.

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

#### **Figure 1.**

*The circulation of dual-Centre theory related to blood glucose on hunger and satiety.*

Energy balance requires an ability of the brain to detect the status of energy stores and match energy intake with expenditure. Dysregulation of appetite and impaired energy expenditure causes excessive food consumption and disrupt the energy balance. In addition, it will cause repeated sense of hunger which contributes to the development of visceral obesity and metabolic syndrome. Frequent intakes of food expose body to store extra calorie which will turn into fat and distribute in different parts of body. There are few hunger hormones known for generating hunger state such as resistin, leptin and ghrelin involve in this process [26]. Previous study mentioned that uncontrolled eating habits like diminishing the frequency of eating, repeated fasting and recurrent over eating were link with obesity-related disorder such as cardiovascular disease, insulin resistance and inflammation [26].
